Abstract: The Purpose of this study is to determine how social and epigenomic factors that are associated with social determinants of health cause increase in Obesity and Comorbidities, resulting in increased risk for breast cancer. Specifically, this study will examine cancer health disparities associated with obesity and other comorbidities in African American and Latina populations residing South Los Angeles. Multiple reasons have been presented in the literature suggesting both socioeconomic and biological phenomena which may contribute to these disparities. Charles R. Drew University of Medicine and Science (CDU) serves the most underserved and under- resourced populations located in the Service Planning Area 6 (SPA6) region of South Los Angeles. Our communities comprise primarily of African Americans (27%) and Latinos (68%). From the residents in SPA6, 31% of the population lives in poverty (household income < 100% federal poverty level (FPL)) and median household income is $36,400, while Los Angeles county is at 17% FPL and with median household income of $56,241. Healthcare and physical environment resources are significantly poor compared to west Los Angeles (SPA5). The Hypothesis and Rationale of this proposed study are: Underserved and Under-resourced communities with poor social determinants of health, are more likely to develop health disparities such as Obesity, Diabetes (T2D), and Hypertension (HTN). These individuals are at increased risk for developing several types of cancers. We will study the incidence and progression of Breast Cancer in these individuals. We will employ biomarkers such as: Sex Hormones, Growth Factors, Inflammatory Cytokines, DNA Methylation, RNA Methylation, and Histone Modifications as they relate to Epigenomic and Genomic changes and their association with risk and clinical outcomes. To accomplish the objectives of our proposal, we will employ the following specific research aims: